A Rare Dichorionic Triamniotic Triplet Pregnancy with Spontaneous Twin Anemia-Polycythemia Sequence between Two Dichorionic Fetuses.

INTRODUCTION: This report presents a rare case of spontaneous twin anemia-polycythemia sequence (TAPS) between two dichorionic fetuses in a spontaneous, homozygotic, dichorionic, triamniotic, triplet pregnancy treated with multiple intrauterine blood transfusions (IUTs) and partial exchange transfusions (PETs). CASE PRESENTATION: The pregnancy was diagnosed with stage IV TAPS at gestational week 25+1. The patient was treated with laser surgery combined with multiple IUTs and PETs. The triplets were delivered at a planned caesarean section at gestational week 28+1 with postnatal hemoglobin values of 18.21, 26.43, and 11.92 g/dL in triplet 1, 2, and 3, respectively. At 4 years of age, triplet 1 is considered healthy, triplet 2 is diagnosed with mild mental retardation, and triplet 3 with profound mental retardation and dystonic cerebral palsy. DISCUSSION: This is an extremely rare case of TAPS between dichorionic fetuses in a triplet pregnancy, and routine surveillance with measurement of middle cerebral artery peak systolic velocity in dichorionic pregnancies may contribute to the detection of similar cases in the future. Furthermore, this case contributes with rare long-term follow-up data of children treated for high-stage TAPS with multiple IUTs and PETs.

Correction: The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight.

[This corrects the article DOI: 10.1371/journal.pmed.1002220.].

Short-Term Flow Changes in Monochorionic Survivor Twins after Ultrasound-Guided Umbilical Cord Occlusion.

OBJECTIVE: To determine hemodynamic changes by Doppler ultrasound of the living fetus during 24 h after umbilical cord occlusion (UCO) in monochorionic diamniotic (MCDA) twin pregnancies. METHOD: We conducted a prospective observational study on fetuses undergoing UCO from 2015 to 2017. Doppler parameters peak systolic velocity (PSV) and umbilical pulsatility index (PI) were obtained in the middle cerebral artery (MCA), umbilical artery (UA) and ductus venosus (DV) before and right after UCO, and at 1, 3, 6, 12, and 24 h after. We used multiple of the median (MoM) to adjust for gestational age. Spaghetti plots visualized flow changes over time. Mixed model adjusting for paired longitudinal data compared the values at different time points. RESULTS: A total of 16 women were included. MCA-PSV dropped within the first hour after surgery from 0.91 to 0.82 MoM (p = 0.08). MCA-PI and UA-PI increased in the first hour from 0.75 to 0.91 MoM (p = 0.02) and 0.94 to 0.98 MoM (p = 0.22), respectively. The DV-PIV increased to 1.14 MoM 3 h after surgery (p = 0.07). The spaghetti plots illustrated the small changes within the first hours and showed a stabilization of flow measurements near initial values 24 h after UCO. CONCLUSION: Within the first hours after UCO the circulation of the survivor twin undergoes small hemodynamic changes.

Refractory Fetal Supraventricular Tachycardia with Hydrops Successfully Converted by Intraperitoneal Flecainide in the Fetus: A Case Report.

INTRODUCTION: Supraventricular tachycardia is the most common fetal tachyarrhythmia and if persistent often associated with fetal hydrops which can cause intrauterine and neonatal death. CASE PRESENTATION: We present a case of early second trimester supraventricular tachycardia in a hydropic fetus, initially refractory to transplacental treatment. CONCLUSION: The supraventricular tachycardia was successfully treated when supplemented with intraperitoneal flecainide in the fetus.

Long-Term Neurodevelopmental Outcome of Monochorionic Twins after Laser Therapy or Umbilical Cord Occlusion for Twin-Twin Transfusion Syndrome.

INTRODUCTION: We sought to assess the incidence of severe neurodevelopmental impairment (NDI) in monochorionic twins treated for twin-twin transfusion syndrome (TTTS) and compare it to the incidence in uncomplicated monochorionic twins. MATERIAL AND METHODS: We included TTTS pregnancies treated by fetoscopic selective laser coagulation (FSLC) or umbilical cord occlusion (UCO) in 2004-2015. Primary outcome was severe NDI defined as cerebral palsy, bilateral blindness or bilateral deafness (ICD-10 diagnoses), and severe cognitive and/or motor delay (assessed by the Ages and Stages Questionnaires [ASQ]). RESULTS: A total of 124 children after TTTS and 98 controls were followed up at 25 months of age (SD 11.4). Severe NDI was found in 8.9% of the TTTS children (10.5% [9/86] after FSLC; 5.3% [2/38] after UCO) compared to 3.1% in the control group (p = 0.10). The odds ratio for severe NDI was 1.8 in cases versus controls (p = 0.37). The total ASQ score was significantly lower in the TTTS group than in controls (p = 0.03) after FSLC (p = 0.03) and after UCO (p = 0.14). DISCUSSION: Children after TTTS appear to have a higher risk of severe NDI and score significantly lower on the ASQ compared to monochorionic twins from uncomplicated pregnancies.

MRI, PET/CT and ultrasound in the preoperative staging of endometrial cancer - a multicenter prospective comparative study.

OBJECTIVES: The aim of this prospective multicenter study was to evaluate and compare the diagnostic performance of PET/CT, MRI and transvaginal two-dimensional ultrasound (2DUS) in the preoperative assessment of endometrial cancer (EC). METHODS: 318 consecutive women with EC were included when referred to three Danish tertiary gynecological centers for surgical treatment. Preoperatively they were PET/CT-, MRI-, and 2DUS scanned. The imaging results were compared to the final pathological findings. This study was approved by the National Committee on Health Research Ethics. RESULTS: For predicting myometrial invasion, we found sensitivity, specificity, PPV, NPV, and accuracy for PET/CT to be 93%, 49%, 41%, 95% and 61%, for MRI to be 87%, 57%, 44%, 92%, and 66% and for 2DUS to be 71%, 72%, 51%, 86% and 72%. For predicting cervical invasion, the values were 43%, 94%, 69%, 85% and 83%, respectively, for PET/CT, 33%, 95%, 60%, 85%, and 82%, respectively, for MRI, and 29%, 92%, 48%, 82% and 78% for 2DUS. Finally, for lymph node metastases, the values were 74%, 93%, 59%, 96%, and 91% for PET/CT and 59%, 93%, 40%, 97% and 90% for MRI. When comparing the diagnostic performance we found PET/CT, MRI and 2DUS to be comparable in predicting myometrial invasion. For cervical invasion and lymph node metastases, however, PET/CT was the best. CONCLUSIONS: None of the modalities can yet replace surgical staging. However, they all contributed to important knowledge and were, furthermore, able to upstage low-risk patients who would not have been recommended lymph node resection based on histology and grade alone.

Fetal ventriculomegaly due to familial submicroscopic terminal 6q deletions.

Submicroscopic terminal 6q deletions are rare. We report on two familial submicroscopic terminal 6q deletions ascertained because of prenatally detected isolated ventriculomegaly and further delineate the variable prenatal and postnatal phenotype. We review published cases of <5 Mb terminal 6q deletions.

Invasive treatment in complicated monochorionic twin pregnancies: indications and outcome of 120 consecutively treated pregnancies.

OBJECTIVE: Monochorionic twin pregnancies are associated with increased risk of severe complications. Umbilical cord occlusion (UCO) and fetoscopic selective laser coagulation (FSLC) are used as invasive treatment. The study aim was to document treatment indications and pregnancy outcome where UCO and FSLC were used for treating fetal discrepancies and twin-to-twin transfusion syndrome (TTTS). DESIGN: Cohort study of all consecutively treated monochorionic twin pregnancies 2004-2010. SETTING: Tertiary care center. POPULATION: One hundred and twenty pregnancies treated by FSLC (55) or UCO (65). Umbilical cord occlusion was undertaken in 49 TTTS cases, in four cases with fetal abnormality and TTTS and in 12 cases because of fetal anomaly only. MAIN OUTCOME MEASURES: Overall survival per fetus, survival per pregnancy of at least one fetus and further survival according to the Quintero stages. Infant survival until at least one week after birth. RESULTS: Of the pregnancies studied, 84% had TTTS, 13% had a fetal malformation and 3% had both. Of TTTS cases, 69% were Quintero stage 3 and 4. In the UCO group with TTTS, 87% were in stage 3 and 4. Survival in the UCO group was 82%. In the laser group, the survival of at least one fetus was 85%. Overall survival per fetus was 60%. CONCLUSIONS: By far the most common indication for invasive treatment was TTTS in Quintero stage 3. Outcome by means of survival after FSLC and UCO were similar to what has been reported elsewhere. Cord occlusion was an acceptable treatment alternative to fetoscopic selective laser coagulation in severe TTTS cases.

Atypical severe intrauterine growth retardation and affected placental function after COVID-19 infection.

This case report describes an atypical progression of pregnancy in a woman who was infected with COVID-19 in her second trimester and initially presented with signs of absent foetal movements. The foetus was diagnosed with severe intrauterine growth restriction and abnormal foetal Doppler flows. The condition slowly improved over months, and the pregnancy was terminated with an acute caesarean section in gestational week 35. Placenta was tested negative for SARS-CoV-2-nucleocapsid. Four days old, the child was found COVID-19-positive, but remained asymptomatic. This case is a rare example considering the improvement of placental function over time.

Menstrual Pattern, Reproductive Hormones, and Transabdominal 3D Ultrasound in 317 Adolescent Girls.

CONTEXT: The knowledge of normal variation of reproductive hormones, internal genitalia imaging, and the prevalence of gynecological disorders in adolescent girls is limited. OBJECTIVE: The study aimed to describe reproductive parameters in postmenarchal girls from the general population including the frequency of oligomenorrhea, polycystic ovary syndrome, and use of hormonal contraception. DESIGN: The Copenhagen Mother-Child Cohort is a population-based longitudinal birth cohort of 1210 girls born between 1997 and 2002. SETTING: University hospital. PARTICIPANTS: A total of 317 girls were included, with a median age of 16.1 years and time since menarche of 2.9 years. MAIN OUTCOME MEASURE(S): Tanner stage, height, weight, age at menarche, menstrual cycle length and regularity, ovarian/uterine volume, and number of follicles were recorded. Serum concentrations of FSH, LH, anti-Müllerian hormone (AMH), inhibin B, estradiol, testosterone, SHBG, androstenedione, dehydroepiandrosterone sulfate, 17-OH-progesterone, and IGF-1 were measured. RESULTS: Twenty girls (6.3%) had oligomenorrhea and differed significantly in serum androgens and AMH, age at and time since menarche from girls with regular cycles. Twenty-seven girls were classified with PCOS (8.5%) and had significantly higher 17-OH-progesterone, estradiol, AMH, LH, and age at menarche than the reference group. Girls on oral contraception had significantly higher serum SHBG concentrations and lower serum concentrations of all hormones except AMH and IGF-1. Ovarian follicles 2 to 29.9 mm correlated positively with serum AMH (P < 0.0001). CONCLUSIONS: Most 16-year-old girls had regular menstrual cycles, normal reproductive hormones, and uterine and ovarian ultrasound. Serum AMH reflected ovarian follicle count and may be a useful biomarker of ovarian reserve.

Uterine volume and endometrial thickness in healthy girls evaluated by ultrasound (3-dimensional) and magnetic resonance imaging.

OBJECTIVE: To report normative data on uterine volume and endometrial thickness in girls, according to pubertal stages; to evaluate factors that affect uterine volume; and to compare transabdominal ultrasound (TAUS) and magnetic resonance imaging (MRI). DESIGN: Cross-sectional study of a nested cohort of girls participating in The Copenhagen Mother-Child Cohort. SETTING: General community. PATIENT(S): One hundred twenty-one healthy girls, aged 9.8-14.7 years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical examination, including pubertal breast stage (Tanner classification: B1-B5). Uterine volume: ellipsoid TAUS (n = 112) and 3-dimensional TAUS (n = 111); ellipsoid MRI (n = 61). Endometrial thickness: TAUS (n = 110) and MRI (n = 60). RESULT(S): Uterine volume and endometrial thickness were positively correlated with pubertal stages; e.g., ellipsoid TAUS: r = 0.753, and endometrium TAUS: 0.648. In multiple regression analyses, uterine volume was associated with the number of large follicles (TAUS >5 mm) (Beta 0.270); estradiol (E2) (Beta 0.504); and height (Beta 0.341). Volumes from ellipsoid vs. 3-dimensional TAUS were strongly correlated (r = 0.931), as were TAUS and MRI: ellipsoid volume (r = 0.891) and endometrial thickness (r = 0.540). Uterine volume was larger in TAUS compared with MRI; mean difference across the measured range: 7.7 (5.2-10.2) cm(3). Agreement was best for small uteri. CONCLUSION(S): Uterine volume and endometrial thickness increased as puberty progressed. Circulating E2 from large follicles was the main contributor to uterine and endometrial growth. The TAUS and MRI assessments of uterus and endometrium were strongly correlated.

Circulating AMH reflects ovarian morphology by magnetic resonance imaging and 3D ultrasound in 121 healthy girls.

CONTEXT: In adult women, Anti-Müllerian hormone (AMH) is produced by small growing follicles, and circulating levels of AMH reflect the number of antral follicles as well as primordial follicles. Whether AMH reflects follicle numbers in healthy girls remains to be elucidated. OBJECTIVE: This study aimed to evaluate whether serum levels of AMH reflects ovarian morphology in healthy girls. DESIGN AND SETTING: This was a population-based cohort study involving the general community. PARTICIPANTS: Included in the study were 121 healthy girls 9.8-14.7 years of age. MAIN OUTCOME MEASURES: Clinical examination, including pubertal breast stage (Tanner's classification B1-5), ovarian volume, as well as the number and size of antral follicles were assessed by two independent modalities: magnetic resonance imaging (MRI), Ellipsoid volume, follicles ≥2 mm; and Transabdominal ultrasound, Ellipsoid and 3D volume, follicles ≥1 mm. Circulating levels of AMH, inhibin B, estradiol, FSH, and LH were assessed by immunoassays; T and androstenedione were assessed by liquid chromatography-tandem mass spectrometry. RESULTS: AMH reflected the number of small (MRI 2-3 mm) and medium (4-6 mm) follicles (Pearson's Rho [r] = 0.531 and r = 0.512, P < .001) but not large follicles (≥7 mm) (r = 0.109, P = .323). In multiple regression analysis, small and medium follicles (MRI ≤ 6 mm) remained the main contributors to circulating AMH (ß, 0.501; P < .001) whereas the correlation between AMH and estradiol was negative (ß, -0.318; P = .005). In early puberty (B1-B3), the number of AMH-producing follicles (2-6 mm) correlated positively with pubertal stages (r = 0.453, P = .001), whereas AMH levels were unaffected (-0.183, P = .118). CONCLUSIONS: Similarly to adult women, small and medium antral follicles (≤6 mm) were the main contributors to circulating levels of AMH in girls.

[Down's syndrome risk assessment in Denmark--secondary publication]. / Risikovurdering for Downs syndrom i Danmark--sekundaerpublikation.

In 2004 The Danish National Board of Health introduced a new guideline regarding prenatal screening. All pregnant women are now offered a Down's syndrome risk assessment. The new guideline has had an impact on the number of invasive early prenatal procedures. The number of procedures fell by 50% from 2000 to 2006. 90% of the foetuses with Down's syndrome are detected prenatally. Denmark is one of the first countries in the world in which risk assessment for Down's syndrome has been successfully implemented at a national level.

[Prenatal diagnosis of chromosome aberrations after implementation of screening for Down's syndrome]. / Praenatal diagnostik af kromosomsygdomme efter indførelse af risikovurdering for Downs syndrom.

INTRODUCTION: First trimester screening for Down's syndrome was evaluated by the National Board of Health in 2004, and recommended to all pregnant women in the form of an informed choice. We have reviewed prenatal and postnatal chromosome aberrations in 3 counties in Denmark during the years of implementation in 2004, 2005 and 2006. MATERIALS AND METHODS: Risk evaluation based on combined screening (fetal nuchal translucency measurement and serum screening of the pregnant woman) was introduced in the counties of Copenhagen, Roskilde and Storstrom, covering approximately 1.1 million inhabitants. We registered the number of chorionic villus biopsies (CVS) and amniocenteses (AC), as well as the number of cases with trisomy, triploidy and sex chromosome aberrations found prenatally. We also registered the number of children born with Down's syndrome during the period. RESULTS: The number of CVS/AC decreased from 1382 to 790, or 40%. There was an increase in the number of foetuses diagnosed with trisomy 21: in 2004 trisomy 21 was diagnosed in 12 foetuses, in 2006 the number was 30. The number of children born with Down's syndrome was 10 and 5 in 2004 and 2006, respectively. National figures from the Danish central cytogenetic registry confirm a decrease in children born with Down's syndrome. CONCLUSION: The implementation of combined screening in 3 counties resulted in a reduction in invasive procedures (chorionic villus samples and amniocenteses) by 40%, which is in accordance with the aims of the National Board of Health. As expected, a significant increase in the number of prenatally diagnosed foetuses with trisomy 21 was observed. The number of children born with Down's syndrome decreased, but the numbers are small. The investigation does not review aspects of organisation or counselling and psychosocial issues.

Prenatal diagnosis of autosomal dominant hereditary spastic paraplegia (SPG4) using direct mutation detection.

OBJECTIVE: To present a report on prenatal diagnosis using direct SPG4 gene analysis in a family with autosomal dominant hereditary spastic paraplegia (AD-HSP). METHODS: Genetic linkage and haplotype analysis were previously carried out with chromosome 2p markers. DNA was obtained from affected individuals, the affected father, the mother, and fetal DNA from an ongoing pregnancy by chorionic villus sampling (CVS) in the first trimester. The spastin gene (SPG4) was completely sequenced. RESULTS: A novel 832insGdelAA frameshift mutation, predicted to cause loss of functional protein, was identified in the affected father and in the fetal DNA. CONCLUSIONS: This is the first report on direct prenatal diagnosis of chromosome 2p-linked AD-HSP (SPG4). In addition, we report a novel SPG4-combined small insertion/deletion mutation in exon 5, which may be the first SPG4 mutational hot spot.